ISSN 0439-755X
CN 11-1911/B

心理学报 ›› 2017, Vol. 49 ›› Issue (10): 1287-1301.doi: 10.3724/SP.J.1041.2017.01287

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 NR3C1基因多态性及单倍型、父母教养方式 对青少年焦虑障碍的影响

 周 雅1,2; 范方1;  彭 婷1;  李媛媛1;   龙 可1;  周洁莹1;  梁颖欣1   

  1.  (1华南师范大学心理学院/华南师范大学心理应用研究中心) (2华南师范大学特殊教育学院, 广州 510631)
  • 收稿日期:2016-08-04 发布日期:2017-08-13 出版日期:2017-10-25
  • 通讯作者: 范方, E-mail: E-mail:E-mail:
  • 基金资助:
     国家自然科学基金面上项目(31271096, 31671165)、国家社会科学基金重大项目(14ZDB159)、教育部人文社会科学重点研究基地重大项目(16JJD190001)、广东省高等学校珠江学者岗位计划资助项目(2016)、中国博士后科学基金面上资助项目(2015M580724)与特别资助项目(2016T90790)。

 The effects of NR3C1 polymorphisms and paternal/maternal parenting styles on Chinese adolescent anxiety disorders

 ZHOU Ya1,2; FAN Fang1; PENG Ting1; LI Yuanyuan1; LONG Ke1; ZHOU Jieying1; LIANG Yingxin1   

  1.  (1 School of Psychology and Center for Studies of Psychological Application, South China Normal University) (2 School of Special Education, South China Normal University, Guangzhou 510631, China)
  • Received:2016-08-04 Online:2017-08-13 Published:2017-10-25
  • Contact: FAN Fang, E-mail: E-mail:E-mail:
  • Supported by:

摘要:  NR3C1参与HPA轴调节, 与应激相关的身心疾病关系密切。以往针对NR3C1与焦虑障碍的研究基本以成人为考察对象, 且大多关注负性生活事件等个体层面环境变量。本研究采用病例−对照设计, 以238名青少年为被试(焦虑障碍117人, 对照121人), 旨在考察NR3C1常见位点rs6191、rs6196、rs41423247的多态性、单倍型以及父母不同类型教养方式对焦虑障碍的影响。结果表明rs6191 GG基因型、rs6196 AA基因型、rs41423247 GG基因型与低焦虑障碍风险相关。父母过多的过度保护与冷漠拒绝、父亲过少的温暖关怀可预测较高的焦虑障碍风险。rs41423247多态性与母亲温暖关怀存在交互作用:rs41423247 GG基因型只在母亲温暖关怀较多时能降低焦虑障碍风险, 在母亲温暖关怀较少时与焦虑障碍并无显著相关。此外, rs6191-rs6196-rs41423247构成的单倍型GAG与低焦虑障碍风险显著关联, TGC与高焦虑障碍风险显著关联, 且二者与母亲温暖关怀、母亲过度保护分别存在交互作用。未来可采用追踪研究, 从表观遗传层面探讨教养方式与NR3C1影响焦虑障碍的内在机制。

关键词: 焦虑障碍, 糖皮质激素受体基因, 教养方式, 基因−环境交互作用

Abstract:  Glucocorticoid receptor gene (NR3C1), one of the key genes involved in the HPA axis regulation, has been evidenced to have a role in various stress-related physical and mental illnesses. Previous studies concerning NR3C1 polymorphisms and anxiety disorders, however, have mostly been conducted among adult samples and looked into negative environmental variables such as adverse or traumatic life events while examining the gene-environment interactions. There is a dearth of knowledge on how NR3C1 polymorphisms could contribute to adolescent anxiety disorders. The purpose of this study was to examine the genetic variants in NR3C1 and their interaction with paternal and maternal parenting styles in relationship to adolescent anxiety disorders using a Chinese sample. This study adopted a case-control design. Of 3501 adolescents underwent a stepwise clinical screening, 117 who were diagnosed with anxiety disorders (74 females; average age 16.69 ± 1.13 years) and 121 healthy controls (56 female; average age 16.54 ± 1.05 years) were included in this study. Participants’ oral mucosal samples were collected for DNA extraction and three single-nucleotide polymorphisms (SNPs) of the NR3C1 gene (i.e., rs41423247, rs6191, rs6196) were genotyped using MassARRAY system. The Chinese version of Parental Bonding Instrument was used to measure four types of paternal/maternal parenting styles (i.e., warmth, autonomy, overprotection, indifference). Multivariate logistic regressions were performed to examine the main effects of genotypes and parental/maternal parenting styles and their interactions in predicting the presence of anxiety disorders. Results revealed that rs6191 GG genotype, rs6196 AA genotype and rs41423247 GG genotype were associated with decreased risk of anxiety disorders. Higher level of paternal/maternal overprotection and indifference, as well as lower level of paternal warmth, could predict increased risk of anxiety disorders. Moreover, there was a significant interaction between rs41423247 genotypes and maternal warmth in predicting adolescent anxiety disorders; that is, rs41423247 GG genotype was linked with reduced risk of anxiety disorders only when maternal warmth was high. Haplotype analysis revealed three haplotypes with frequencies of > 5% (rs6191-rs6196-rs41423247): GAG, TAC, and TGC. GAG and TGC were respectively associated with decreased and increased risk of anxiety disorders. Maternal warmth and overprotection were found to moderate these effects. GAG would reduce the risk of anxiety disorders only when maternal warmth was high, while TGC would enhance the risk only when maternal overprotection was high. This study is the first to investigate the role of NR3C1 polymorphisms and parenting styles in anxiety disorders among Chinese adolescents. The findings on gene-environment interactions lend support to the vantage sensitivity hypothesis, which propose variation in people’s responsiveness to exclusively positive environmental influences as a function of individual endogenous characteristics. Future research on the epigenetic mechanisms underlying the relationship between NR3C1, parenting styles and adolescent anxiety disorders is warranted, to further explore the disease etiology.

Key words:  anxiety disorders, glucocorticoid receptor gene, parenting styles, gene-environment interaction